Optogenetics Device Offers Stable Way to Treat Bladder Problems

A tiny, implantable device has been introduced that can detect overactivity in the bladder and use light from biointegrated LEDs to tamp down the urge to urinate. The device has been demonstrated in laboratory rats and could one day be used to treat overactive bladder, urinary incontinence, and interstitial cystitis in people. It was created by a team of neuroscientists and engineers at the Washington University School of Medicine, the University of Illinois at Urbana-Champaign, and the Feinberg School of Medicine at Northwestern University.

The researchers implanted a soft, stretchy beltlike device around the bladder of the lab rats. The device expanded and contracted as the bladder filled and emptied. The team also injected proteins called opsins into the animals’ bladders. The opsins were carried by a virus that binds to nerve cells in the bladder, making those cells sensitive to light signals. The device used an optical stimulation interface to cause microscale inorganic LEDs to activate the opsins.

This CT scan of a rat shows a small device implanted around the bladder. The device — developed by scientists at Washington University School of Medicine in St. Louis, the University of Illinois, and Northwestern University — uses light signals from tiny LEDs to activate nerve cells in the bladder and control problems such as incontinence and overactive bladder. Courtesy of Gereau Lab, Washington University.

A soft, high-precision biophysical sensor system allows continuous measurements of organ function. A control module and data analytics enable the coordinated, closed-loop operation of the system to eliminate pathological behaviors as they occur. The researchers use Bluetooth communication to signal an external hand-held device, and read information from the implant in real time. A simple algorithm is used to detect when the bladder is full, when the animal has emptied its bladder, and when bladder emptying is occurring too frequently. The device delivers therapy only when it detects a problem. Once the behavior is normalized, the micro-LEDs are turned off.

“When the bladder is emptying too often, the external device sends a signal that activates micro-LEDs on the bladder band device, and the lights then shine on sensory neurons in the bladder,” professor Robert Gereau said. “This reduces the activity of the sensory neurons and restores normal bladder function.”

The researchers, who plan to test similar devices in larger animals, believe a comparable strategy could work in people. Devices for people could be implanted using catheters to place them through the urethra into the bladder.

“This example brings together the key elements of an autonomous, implantable system that can operate in synchrony with the body to improve health: a precision biophysical sensor of organ activity; a noninvasive means to modulate that activity; a soft, battery-free module for wireless communication and control; and data analytics algorithms for closed-loop operation,” said professor John Rogers.

For about 30 years, severe bladder problems often have been treated with electrical stimulators that send a current to the nerve that controls the bladder. Such implants improve overactive bladder, but can disrupt normal nerve signaling to other organs. “There definitely is benefit to that sort of nerve stimulation, but there also are some off-target side effects that result from a lack of specificity with those older devices,” Gereau said.

The team’s all-optical scheme for neuromodulation could offer chronic stability and the potential to stimulate specific cell types. The researchers believe their approach could be used in other parts of the body — to treat chronic pain or stimulate cells in the pancreas to secrete insulin, for example.

One hurdle, however, involves the viruses used to get the light-sensitive proteins to bind to cells in organs. “We don’t yet know whether we can achieve stable expression of the opsins using the viral approach and, more importantly, whether this will be safe over the long term,” Gereau said. “That issue needs to be tested in preclinical models and early clinical trials to make sure the strategy is completely safe.”

The research was published in Nature (https://doi.org/10.1038/s41586-018-0823-6).